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Biomedical subjects

S Sawai

Publications and source records attributed to S Sawai.

At least 19 recordsLinked to original sources

Analysis of MUC4 mucin expression in lung carcinoma cells and its immunogenicity.

BACKGROUND: MUC4 has been cloned from tracheobronchial mucosa cDNA and reportedly is highly expressed in some human malignancies, including lung carcinoma. However, little is known about molecular and biologic characteristics. The authors analyzed expression levels of MUC4 mRNA and protein in lung carcinoma cells and analyzed the immunogenicity of this mucin. METHODS: Nine cultured lung carcinoma cell lines and 29 tumor samples from patients with lung carcinoma were examined by Northern hybridization for MUC4 mRNA expression and by flow cytometry or an immunohistochemical staining for its protein expression. Sera from the patients were examined for their reactivity with MUC4 by enzyme-linked immunosorbent assay. RESULTS: Forty-four percent of the cell lines and 72% of the tumor samples showed high levels of MUC4 mRNA expression. Although MUC4 protein was not detected in any live carcinoma cell lines by flow cytometry using rabbit antisera reactive with the MUC4 core, pretreatment with paraformaldehyde and sialidase resulted in successful detection of the protein in 50% of the cell lines. An immunohistochemical study revealed that 67% of the tumors exhibited MUC4 protein expression without any digestion. In 29% of the patients, high levels of anti-MUC4 immunoglobulin M or immunoglobulin G were detected. CONCLUSIONS: MUC4 protein expression was elevated in lung carcinoma tissues because of the increase in its mRNA expression and deglycosylation on its core. This mucin is sufficiently immunogenic to elicit humoral and cellular immunity specific for MUC4 in patients with malignant disease. MUC4 is expected to be useful as a target antigen in immunotherapy for patients with carcinoma of the lung.

Biomarkers, Tumor↗

The elusive benzocyclobutenylidene: a combined computational and experimental attempt.

Ab initio and density functional theory calculations predict that benzocyclobutenylidene (1) has a singlet ground state in contrast to the parent phenylcarbene and many other simply substituted arylcarbenes. Calculations also predict that 1 should lie in a relatively deep potential well, while its triplet state is 14.5 kcal mol(-)(1) higher in energy. However, attempts to observe 1 directly by photolysis of two different nitrogenous precursors were not successful. Irradiation of diazobenzocyclobutene (7) (lambda > 534 nm or lambda > 300 nm) or azibenzocyclobutene (10) (lambda > 328 nm) in Ar matrixes at 10 K leads to the formation of the strained cycloalkyne 7-methylenecyclohepta-3,5-dien-1-yne (3). (13)C-Labeled 3 was also prepared in a similar manner. There is very good agreement between experimental IR spectra and computationally derived harmonic vibrational frequencies for 3 and [(13)C]-3 and excellent agreement between observed and calculated isotopic shifts. Prolonged short-wavelength irradiation converts 3 into benzocyclobutadiene (5). Phenylacetylene (6) and benzocyclobutadiene dimer (11) were identified as products arising from flash vacuum pyrolysis of diazirine 10 at 500 degrees C.

Journal Article↗

Periosteal chondroma of the rib: report of two cases.

We report two cases of periosteal chondroma of the rib, an extremely rare entity. The first case involved a 5-year-old boy who was admitted with pain and swelling around his left fifth rib. Surgery was performed in May 1999, and an 8 x 6 x 5 mm tumor was resected with the fifth rib. The second case involved a 39-year-old man with a 2-month history of cough who was referred to our department after a coin lesion had been detected on a chest roentgenogram. Physical examination on admission did not reveal any pain or tenderness. The rib tumor was resected along with the fourth rib by video-assisted thoracoscopic surgery and minithoracotomy in February 2000. The tumor was well encapsulated and consisted of an elastic hard mass measuring 22 x 15 x 13 mm. Both patients had an uneventful postoperative course and have remained well with no evidence of recurrence. Our review of the literature revealed only six previously documented cases of periosteal chondroma of the rib.

Adult↗

Transmission electron microscopy of fine aromatic hydrocarbon particles.

Fine perylene and pyrene particles were produced by evaporation in helium gas. The particles were sensitive to electron beam radiation. The pyrene particles sublimed under observation. These difficulties were cleared up by reducing electron beam exposure and sandwiching a specimen between two Formvar films. The fine perylene particles were rectangular or hexagonal plates about 50nm thick. The size was about 200-2000nm. The fine pyrene particles were polymorphic with a size of about 300-2000nm. The crystal forms of the perylene and pyrene particles were determined from the electron diffraction patterns to be alpha-perylene and pyrene I, respectively.

Journal Article↗

Involvement of granzyme B and perforin in suppressing nodal metastasis of cancer cells in breast and lung cancers.

AIMS: Granzyme B and perforin, which are contained in cytotoxic granules produced by tumour-infiltrating immune cells, have been reported to be involved in suppression of cancer progression. In this study, the relationship between expression of these molecules and clinical factors in cancer patients was studied. METHODS: Tumour tissue obtained from 23 breast cancer patients and 13 lung cancer patients were examined for expression of granzyme B, perforin and B7-1, using an immunohistochemical technique. The percentage of cells positive for expression of these molecules and the clinical status of each case were compared. RESULTS: Both granzyme B and perforin were distributed in the cytoplasm of cancer cells in many cases rather than in tumour-infiltrating lymphocytes. This was observed even in cases of early-stage tumours. In both breast and lung cancer patients, the percentage of cells positive for granzyme B and perforin expression was inversely correlated with the status of regional node metastasis. A competitive RT-PCR analysis confirmed that the expression of mRNA from these molecules extracted from the tumours was consistent with the immunohistochemical results. CONCLUSION: Granzyme B and perforin may play a role in the suppression of nodal metastasis of cancer cells in breast and lung cancers.

Aged↗

Spontaneous symmetry breaking turing-type pattern formation in a confined Dictyostelium cell mass.

We have discovered a new type of patterning which occurs in a two-dimensionally confined cell mass of the cellular slime mold Dictyostelium discoideum. Besides the longitudinal structure reported earlier, we observed a spontaneous symmetry breaking spot pattern whose wavelength shows similar strain dependency to that of the longitudinal pattern. We propose that these structures are due to a reaction-diffusion Turing instability similar to the one which has been exemplified by CIMA (chlorite-iodide-malonic acid) reaction. The present finding may exhibit the first biochemical Turing structure in a developmental system with a controllable boundary condition.

Animals↗

Reexpansion pulmonary edema due to high-frequency jet ventilation: report of a case.

Barotrauma is well known to be a relatively common complication of high-frequency jet ventilation (HFJV); however, the occurrence of reexpansion pulmonary edema (REPE) is extremely rare. We report herein a case of REPE caused by difficulties encountered with anesthesia using HFJV during video-assisted thoracic surgery (VATS) for a spontaneous pneumothorax. We believe the rapid increase in pressure in the lung after degassing for VATS resulted in REPE as well as typical barotrauma.

Adolescent↗

Encapsulated pericardial fat necrosis treated by video-assisted thoracic surgery: report of a case.

A 55-year-old moderately obese man who was admitted to a local hospital following a traffic accident reported having experienced an episode of sharp and sudden pleuritic pain in the left anterior lower chest 2 days earlier. A computed tomographic scan on admission demonstrated a nonhomogeneous mass in the anterior left side of the chest, abutting the left cardiac margin, and a left-sided pleural effusion. As a mediastinal tumor was suspected, he was referred to our hospital for investigation and treatment. An exploratory thoracotomy was performed by video-assisted thoracic surgery (VATS) about 3 weeks later, which revealed a firm, yellowish mass on the oral side of the pericardial fat pad, adhering to the anterior chest wall. The mass was easily removed. The resected specimen consisted of a lobulated fragment of adipose tissue measuring 5.0 x 3.5 x 2.0 cm, and the final pathologic diagnosis was pericardial fat necrosis. The patient had an uneventful postoperative recovery and has remained free of symptoms for 10 months since his operation. Pericardial fat necrosis remains a rare clinical entity. Surgical excision by VATS achieves symptomatic cure and probably continues to be the treatment of choice because of the need to exclude a neoplasm in the differential diagnosis.

Diagnosis, Differential↗

Diploid/triploid mosaic placenta with fetus. Towards A better understanding of 'partial moles'.

We describe a case of partial molar change in a placenta that was associated with a normal female fetus who died in utero. The analysis of molar and normal placental tissue, as well as the karyotypic study of amnionic fluid indicate a complex origin of this conceptus. We review the possible mechanisms leading to this pregnancy and the general topic of partial hydatidiform mole. The formation of moles is complex and it is not easily divisible into so-called partial and complete hydatidiform moles. Rather, individual genetic study is needed to make an accurate diagnosis because macroscopic or microscopic examination alone fails to assess the complexity of these entities.

Adult↗

A case of Meniere's disease with vertical nystagmus after administration of glycerol.

A 62-year-old woman who complained of repetitive vertigo with a left fluctuating hearing loss was admitted to our hospital three times. A glycerol test was done on the third admission. Two hours after the administration of glycerol, the patient complained of rotatory vertigo with a downbeat vertical nystagmus. This nystagmus then changed its direction upward. Her left hearing loss was improved during the glycerol test. On the day after the glycerol test, a caloric test was done. The caloric response of the right ear was remarkably improved. Although she had not felt a hearing loss in the right ear, an overwritten audiogram showed a fluctuation of hearing in the right ear. The bilateral caloric responses fluctuated. From these findings, it appears that the function of the inner ear on both sides fluctuating. We speculate that the administration of glycerol elicited an asymmetry in the function of the inner ear on both sides and ocuured vertigo with vertical nystagmus because of the irritation of both ears.

Audiometry↗

Rapid patterning in 2-D cultures of Dictyostelium cells and its relationship to zonal differentiation.

Rapid patterning has been observed in confined 2-D cultures of Dictyostelium discoideum Ax-2 cells as an outer dark zone and a inner light zone. The width of outer zone was usually approximately100 microm, irrespective of the size of cell masses under atmospheric conditions. The width of the outer zone, however, changed depending on external O2 concentrations and reached up to 250 microm at 100% O2. A clear regional difference in tetramethyl rhodamine methyl ester (TMRM) staining was noticed between the outer zone and the inner zone: the inner zone was more strongly stained with TMRM than the outer zone, which faced the air. Using inhibitors of oxidative phosphorylation (dinitrophenol (DNP) or NaN3) and a specific inhibitor of CN-resistant respiration (benzohydroxamic acid (BHAM)), it has been demonstrated that the outer zone is basically formed by the O2 threshold for oxidative phosphorylation, while the inner cells mainly perform cyanide-resistant respiration. When cells around the early mound stage (just before prestalk and prespore differentiation) were cultured as 2-D cell masses, ecmA-expressing cells (pstA cells), ecmB-expressing cells (pstB cells) and D19-expressing cells (prespore; psp cells), arose in a position-dependent manner in the outer zone. In the inner zone, cell motility seemed to be markedly impaired and neither prestalk nor prespore differentiation occurred. In addition, once-differentiated prespore cells were found to dedifferentiate rapidly in the inner zone. The reason for dedifferentiation as well as for failure of cells to differentiate in the inner zone is discussed with reference to O2 radicals.

Animals↗

Results of combined resection of adjacent organs in lung cancer.

BACKGROUND: Indications for surgical treatment in advanced lung cancer still remain to be established. METHODS: The outcomes of combined resection of adjacent organs in lung cancer were assessed in terms of complications and the invasiveness of surgery, using intraoperative blood loss and operation time as indices. RESULTS: In 68 patients undergoing combined resection between 1980 and 1997, the 5-year-survival rates and the incidence of complications and hospital deaths were 24.5%, 52.9%,and 10.3%, respectively. The mean blood loss and operation time were 1,200 ml and 396 minutes. The rares of complications and hospital deaths were significantly higher in the group with 1,000 ml or more blood loss, and in the group with 360 minutes or longer operation time. CONCLUSIONS: In terms of the survival rate, invasiveness of surgery, and complications, the pleura and pericardium were the best indications for combined surgery. For the thoracic wall, blood loss was greater and the rates of complications and hospital deaths tended to be higher among T3 cases. Both blood loss and operation time tended to be greater in T4 cases. Indications for surgery need to be carefully determined with respect to curability.

Adult↗

HES-1 repression of differentiation and proliferation in PC12 cells: role for the helix 3-helix 4 domain in transcription repression.

HES-1 is a Hairy-related basic helix-loop-helix protein with three evolutionarily conserved regions known to define its function as a transcription repressor. The basic region, helix-loop-helix domain, and WRPW motif have been characterized for their molecular function in DNA binding, dimer formation, and corepressor recruitment, respectively. In contrast, the function conferred by a fourth conserved region, the helix 3-helix 4 (H-3/4) domain, is not known. To better understand H-3/4 domain function, we expressed HES-1 variants under tetracycline-inducible control in PC12 cells. As expected, the induced expression of moderate levels of wild-type HES-1 in PC12 cells strongly inhibited nerve growth factor-induced differentiation. This repression was dependent on the H-3/4 domain. Unexpectedly, expression of HES-1 also arrested cell growth, an effect that could be reversed upon down regulation of HES-1. Concomitant with growth arrest, there was a strong reduction in bromodeoxyuridine incorporation and PCNA protein levels, although not in cyclin D1 expression. Expression of a HES-1 protein carrying the H-3/4 domain, but not the WRPW domain, still partially inhibited both proliferation and differentiation. Transcription assays in PC12 cells directly demonstrated that the H-3/4 domain can mediate DNA-binding-dependent transcription repression, even in the absence of corepressor recruitment by the WRPW motif. HES-1 expression strongly repressed transcription of the p21(cip1) promoter, a cyclin-cyclin-dependent kinase inhibitor up regulated during NGF-induced differentiation, and the H-3/4 domain is necessary for this repression. Thus, the H-3/4 domain of HES-1 contributes to transcription repression independently of WRPW function, inhibits neurite formation, and facilitates two distinct and previously uncharacterized roles for HES-1: the inhibition of cell proliferation and the direct transcriptional repression of the NGF-induced gene, p21.

Animals↗

[Squamous cell type lung cancer that produced granulocyte colony-stimulating factor].

A 73-year-old man was hospitalized because of weight loss and fever. Laboratory data showed marked leukocytosis (21,200/mm3), granulocytosis (89.7%), thrombocytosis (47.8 x 10(4)/mm3), increased CRP (15.8 mg/dl), and increased SCC (5.0 ng/ml). Chest X-ray films demonstrated a mass shadow in the right upper lung field. Chest computed tomographic scans revealed a mass shadow 58 mm in diameter with mediastinal pleural invasion in the right S1. Right upper lobectomy and dissection of regional lymph nodes was performed under a diagnosis of lung cancer (squamous cell carcinoma, T3 N0 M0 stage IIB) with concomitant infection. Serum G-CSF was 234 pg/ml pre-operatively and 68.8 pg/ml postoperatively. The cytoplasm of tumor cells stained positively with anti-recombinant human G-CSF monoclonal antibody. No general bacteria or mycobacteria were detected within the specimen. Postoperatively, the patient's white blood cell count, platelet count, and CRP level soon decreased, and the fever disappeared. We diagnosed the disease as G-CSF-producing squamous cell type lung cancer.

Aged↗

Autologous dendritic cells or cells expressing both B7-1 and MUC1 can rescue tumor-specific cytotoxic T lymphocytes from MUC1-mediated apoptotic cell death.

We attempted to induce MUC1-specific cytotoxic T lymphocytes (CTLs) by mixed-lymphocyte tumor cell culture (MLTC) using two allogeneic MUC1-positive cancer cell lines, T-47D and MCF7. The induced CTLs exhibited MUC1-specific cytotoxicity 16 days after the initial stimulation. However, these CTLs underwent apoptotic death within 16 days. To examine whether the B7-1 molecule is required for the expansion of the responder cells, a B7-1(+)/MUC1(-) cell line was transfected with MUC1 cDNA, and the resulting transfectant was employed as a stimulator in an autologous MLTC. The CTLs exhibited MUC1 specificity but also continued to propagate. In parallel, autologous dendritic cells (DCs) were added to an MLTC containing peripheral blood lymphocytes (PBLs) and the allogeneic MUC1-positive stimulators. The CTLs demonstrated MUC1 specificity and their number increased. This suggests that the B7-1 molecule is required for rescuing CTLs from MUC1-mediated apoptotic death, but not for the induction of MUC1-specific responsiveness. This strategy to obtain the CTLs efficiently may be useful for adoptive immunotherapy against cancer.

Antigen Presentation↗

Autonomic nervous function in patients with Meniere's disease evaluated by power spectral analysis of heart rate variability.

OBJECTIVE: A hypothesis has been advanced that the autonomic nervous dysfunction (AND) relates to the development of vertigo in Meniere's disease (MD). We also studied the causal relationship between AND and vertigo in MD. METHODS: We evaluated autonomic nervous function in 17 patients with MD (five men and 12 women ranging in age from 16 to 70 years) by classifying them by their stages of attack and interval of vertigo and with power spectral analysis (PSA) of heart rate variability. Fourteen healthy volunteers were also tested as controls. RESULTS: At the interval stage, parasympathetic nervous hypofunction and significant depression of sympathetic response due to postural changes from the supine to the standing position were observed in many of those patients. At the attack stage, sympathetic nervous hypofunction was observed in some of the patients. CONCLUSION: These findings lead us to the conclusion that AND relates to vertigo in MD as a predisposing factor. However, the question of whether AND relates as a trigger or as a consequence of vertigo in MD has not been adequately solved in this study. We will make further studies on circadian variation of autonomic nervous function.

Adolescent↗

Physical development of surgically treated patients with primary spontaneous pneumothorax.

STUDY OBJECTIVES: There have been many studies on the physical characteristics at the time of contraction of a primary spontaneous pneumothorax (PSP), but it has not been shown when and how such physical characteristics develop. These issues were investigated. PATIENTS AND DESIGN: Physical development of 27 male patients with PSP were examined. Their physical records were collected with the patients' permission, and standard curves, estimated from the Japanese nationwide records in the year corresponding to the ages of the patients, were plotted as control values. RESULTS: The height of patients was already greater at 6 years of age. It showed a marked increase from 11 to 14 years. The body weight was more than the standard until 9 years, but it became less after age 11, and this difference increased after age 15. Rohrer's index was significantly lower than the standard at all ages, and the difference was particularly large from 11 to 15 years. In the standard group, there was a balance between the annual height and weight gain. In the patient group, annual weight gain was similar to that in the standard group whereas height began to increase 2 years earlier, and as a result, ectomorphy, which was also observed before this age, became marked at this age. CONCLUSIONS: The rapid increase in the vertical dimension of the thorax compared with the horizontal dimension during the period of rapid physical development is considered to affect intrathoracic pressure at the apex of lung, which would have some influence on enhancing cyst formation.

Adolescent↗

[Prognostic significance of EGFR and p53 expression, and angiogenesis in laryngeal squamous cell carcinoma].

PURPOSE: To estimate the influence of EGFR, p53, and angiogenesis to the survival of laryngeal cancer patients. PATIENTS: Ninety-seven laryngeal cancer patients who received initial treatment at Gifu University Hospital from 1986 to 1996. Patients were classified as follows: T2, 51; T3, 35; T4, 13. METHOD: Using monoclonal antibodies against EGFR, p53, and factor VIII, respectively, immunohistochemical staining was performed on surgically obtained biopsy specimens. Univariate and multivariate regression analyses in accordance with Cox proportional hazards model were performed to adjust for the possible confounding effects and interactions of each factor. Three different end points, i.e. any death, cancer-related death, and cancer relapse (either local recurrence or distant metastasis), were used to evaluate overall survival, cause-specific survival, and relapse-free survival, respectively. RESULT: In univariate analysis, sex (P = 0.0052), age (P = 0.0038), T stage (P = 0.0096) and N stage (P = 0.0261) were significantly correlated with overall survival; sex (P = 0.0076), T stage (P = 0.0167) and factor VIII expression (P = 0.0443) were related to cause-specific survival; T stage (P = 0.0005) and EGFR expression (P = 0.0103) were related to relapse-free survival. In multivariate analysis, supraglottis (P = 0.0296) and factor VIII expression (P = 0.0345) were significantly correlated with overall survival; supraglottis (P = 0.0333), T stage (P = 0.0179) and factor VIII expression (P = 0.0134) were significantly correlated with cause-specific survival; T stage (P = 0.0166), chemotherapy (P = 0.0087) and EGFR expression (P = 0.0016) were significantly correlated with relapse-free survival. CONCLUSION: The present study confirmed that multivariate analysis in accordance with the Cox proportional hazards model revealed that angiogenesis was an independent predictor of overall survival and cause-specific survival, and that EGFR expression was an independent predictor of relapse-free survival in patients with T2, T3 or T4 laryngeal cancer.

Aged↗