Quantifying the uncertainty of spontaneous Ca2+ oscillations in astrocytes: particulars of Alzheimer's disease.

The quantification of spontaneous calcium (Ca(2+)) oscillations (SCOs) in astrocytes presents a challenge because of the large irregularities in the amplitudes, durations, and initiation times of the underlying events. In this article, we use a stochastic context to account for such SCO variability, which is based on previous models for cellular Ca(2+) signaling. First, we found that passive Ca(2+) influx from the extracellular space determine the basal concentration of this ion in the cytosol. Second, we demonstrated the feasibility of estimating both the inositol 1,4,5-trisphosphate (IP(3)) production levels and the average number of IP(3) receptor channels in the somatic clusters from epifluorescent Ca(2+) imaging through the combination of a filtering strategy and a maximum-likelihood criterion. We estimated these two biophysical parameters using data from wild-type adult mice and age-matched transgenic mice overexpressing the 695-amino-acid isoform of human Alzheimer ß-amyloid precursor protein. We found that, together with an increase in the passive Ca(2+) influx, a significant reduction in the sensitivity of G protein-coupled receptors might lie beneath the abnormalities in the astrocytic Ca(2+) signaling, as was observed in rodent models of Alzheimer's disease. This study provides new, to our knowledge, indices for a quantitative analysis of SCOs in normal and pathological astrocytes.

[Three primary cancers of pulmonary cancer, malignant melanoma and esophageal cancer; report of a case].

A 61-year-old man, who had medical history of hepatitis type C, surgery for malignant melanoma of the lower limb, endoscopic mucosal resection for esophageal cancer, was pointed out a pulmonary nodule in the right middle lobe by surveillance computed tomography after 5 years of surgery for melanoma. Pathology of esophageal cancer was squamous cell carcinoma limited in mucosa without lymphatic nor venous invasion. The nodule gradually enlarged and respiratory endoscopic examination could not establish pathological diagnosis. Thoracoscopy-assisted pulmonary biopsy revealed squamous cell carcinoma, and right middle lobectomy with mediastinal node dissection was performed. Histological examination showed moderately differentiated squamous cell carcinoma without lymph node involvement. The stage of lung cancer was T1N0M0, stage IA. Although 9 months have passed since surgery for lung cancer, recurrence of each malignancy has not been detected.

Multiphoton fluorescent images with a spatially varying background signal: a ML deconvolution method.

By means of multiphoton laser scanning microscopy, neuroscientists can look inside the brain deeper than has ever been possible before. Multiphoton fluorescent images, as all optical images, suffer from degradation caused by a variety of sources (e.g. light dispersion and absorption in the tissue, laser fluctuations, spurious photodetection and staining deficiency). From a modelling perspective, such degradations can be considered the sum of stochastic noise and a background signal. Among the methods proposed in the literature to perform image deconvolution in either confocal or multiphoton fluorescent microscopy, Vicidomini et al. (2009) were the first to incorporate models for noise (a Poisson process) and background signal (spatially constant) in the context of regularized inverse problems. Unfortunately, the so-called split-gradient deconvolution method (SGM) they used did not consider possible spatial variations in the background signal. In this paper, we extend the SGM by adding a maximum-likelihood estimation step for the determination of a spatially varying background signal. We demonstrate that the assumption of a constant background is not always valid in multiphoton laser microscopy and by using synthetic and actual multiphoton fluorescent images, we evaluate the face of validity of the proposed method, and compare its accuracy with the previously introduced SGM algorithm.

Modeling the spontaneous Ca2+ oscillations in astrocytes: Inconsistencies and usefulness.

Spontaneous calcium (Ca2+) oscillations (SCOs) in astrocytes might be a crucial signaling for the multipurpose role of this type of cell in several brain functions. To interpret experimental data of astrocytic SCOs, which has been largely observed in the last decade, several groups have attempted to accommodate biophysical models that were developed in the past for Ca2+ signaling in other cell types. In most of the cases, only predictive strategies were used to estimate specific parameters of these modified models from actual experiments. In this study, we discuss the most remarkable models used to describe Ca2+ signaling in astrocytes. At the same time, we aim to revise the particulars of applying these models to interpret epifluorescent time series obtained from large regions of interest. Specially, we developed a detailed model for global Ca2+ signaling in the somata of astrocytes. In order to estimate some of the parameters in our model, we propose a deductive reasoning strategy, i.e., a statistical inference method that results from combining a filtering technique and a maximum likelihood principle. By means of computer simulations, we evaluate the accuracy of this estimation's strategy. Finally, we use the new model, in combination with a recent experimental findings by our group, to estimate the degree of cluster coupling inside the soma during the genesis of global Ca2+ events.

[Assessment of surgical treatment for lung cancer with pericardial or left atrial invasion].

We evaluated surgical results for the patients who underwent pulmonary resection combined with pericardial or left atrial resection due to locally advanced non-small cell lung cancer (NSCLC). Seven patients who underwent pericardial resection (T3 group) and 4 patients who underwent resection of the left atrium (T4 group) were included in this study, and clinical findings and prognosis were evaluated. Eight patients underwent pneumonectomy, and others underwent lobectomy or bilobectomy. Histology of the cancer was squamous cell carcinoma in all patinets. As for pathological node involvement, N0/N1 disease was 72.7% and N2 disease was 27.3%. Induction chemotherapy was performed in 75.0% of T4 group. Adjuvant chemotheraphy was performed in 71.4% of T3 group and 75.0% of T4 group. Five-year-survival was 57.1% in T3 group and 25.0% in T4 group. Five-year-survival was 62.5% in N0/N1 disease and 0% in N2 disease. Statistical significance in prognosis was seen in lymph node status (p = 0.0317). Extended resection of pericardium or left atrium for patients with N2 disease of NSCLC is not recommended. When invasion to pericardium or left atrium is diagnosed during surgery, extended resection should be indicated in patient without N2 metastasis.

Cytocompatibility of calcium phosphate coatings deposited by an ArF pulsed laser.

In the current studies, we deposited ultra-thin hydroxyapatite films on a pure titanium substrate by pulsed laser deposition, and we examined the effects of these surfaces on rat bone marrow (RBM) cells. This method allowed deposition of 500-, 2,000-, and 5,000-A-thick hydroxyapatite films. X-ray diffraction showed that the amorphous films recrystallized to a hydroxyapatite crystal structure after annealing. The proliferation of RBM cells was unaffected by the hydroxyapatite films, but osteocalsin and alkaline phosphatase mRNA and protein levels were elevated in cells grown on 2,000- and 5,000-A-thick films. These results indicate that ultra-thin hydroxyapatite films generated by pulsed laser deposition are better at promoting osteogenesis than pure titanium surfaces.

Cytocompatibility of calcium phosphate coatings deposited by an ArF pulsed laser.

In the current studies, we deposited ultra-thin hydroxyapatite films on a pure titanium substrate by pulsed laser deposition, and we examined the effects of these surfaces on rat bone marrow (RBM) cells. This method allowed deposition of 500-, 2000-, and 5000-Angstrom-thick hydroxyapatite films. X-ray diffraction showed that the amorphous films recrystallized to a hydroxyapatite crystal structure after annealing. The proliferation of RBM cells was unaffected by the hydroxyapatite films, but osteocalsin and alkaline phosphatase mRNA and protein levels were elevated in cells grown on 2000- and 5000-Angstrom-thick films. These results indicate that ultra-thin hydroxyapatite films generated by pulsed laser deposition are better at promoting osteogenesis than pure titanium surfaces.

[Congenital esophagobronchial fistula treated with thoracoscopic assisted surgery].

A case of congenital esophagobronchial fistula in a 58-year-old woman was described. The patient had presented with repeated attacks of pulmonary infection from her childhood and had a history of recurrent cough after eating or drinking. Preoperative examinations including esophagogram by barium swallow revealed existence of a fistula between the upper thoracic esophagus and the right B3 bronchus. The fistula was recognized as type I of Braimbridge classification. Thoracoscopic assisted fistulectomy and diverticulectomy for esophagobronchial fistula with esophageal diverticulum were performed. The neck of the diverticulum and the fistula were divided with endo-stapling technique. Intraoperative esophagoscopy was found to be useful for the definite localization and complete excision of the fistula and the diverticulum and the avoidance of stenosis of the esophagus. Postoperative course was uneventful. It is to be considered that the present thoracoscopic assisted procedure with intraoperative esophagoscopy can be used as a standard operative procedure for esophagobronchial fistula with esophageal diverticulum.

[A case of squamous cell carcinoma of the lung associated with exophthalmos and hypercalcemia].

A 69-year-old man visited in the department of ophthalmology of this university, complained with exophthalmos. He was pointed out hypercalcemia and transferred to the department of endocrinology. The chest X-ray and thoracic CT showed a large mass in lower lobe of the left lung. Cytological diagnosis of this tumor was squamous cell carcinoma. In clinical examination, serum CA was 12.2 mg/dl in spite of normal level of PTH, calcitonin, 1 alpha, -25 (OH) 2D3 and uric cAMP. On the other hand, PTHrP-intact in serum was 9.8 pmol/l. His thyroid gland had no abnormality in palpation or roentogenological examination. The thyroid functions, thyroglobulin, thyrotropin receptor antibody, thyroid test and microsome test were all in normal limit. From these results, he was diagnosed of lung cancer with humoral hypercalcemia of malignancy and euthyroid "isolated" Graves' ophthalmopathy. Left lower lobectomy with mediastinal lymph node dissection (R 2 a) was done and p-stage was IIIA. After operation, serum Ca decreased in normal level and the exophthalmos was also improved gradually. He was in well until 10 months after operation, and died with multiple lung metastases and hypercalcemia. Exophthalmos was also recurred in his terminal stage. Similar case could not find in literature and some discussion of the literatures was mentioned.

[Preoperative evaluation of the right ventricular function using the pulsed Doppler echocardiogram in the patients scheduled for the elective pulmonary resection].

Preoperative evaluation of the both right ventricular (RV) systolic and diastolic function using the pulsed Doppler echocardiogram were examined for 46 patients scheduled for the pulmonary resection of the pulmonary tumorous lesions. The parameters which included the RV inflow pattern at the tricuspid orifice and the RV ejection flow pattern at the RV outflow tract were obtained by the pulsed Doppler echocardiogram. Following results were obtained. 1) The RV afterload shown by the parameters of the acceleration time (AT, time beginning of RV ejection to peak velocity) were higher in the aged patients, the low FEV 1% populations, and the patients having the deteriorated left ventricular contraction. 2) The RV diastolic dysfunction were present preoperatively in aged patients over the 60 years old. This phenomenon was characterized by a high degree of atrial contraction and an increased ratio of the peak velocity in atrial contraction phase to that in early rapid filling phase (A/E). When we evaluate the RV inflow and ejection Doppler flow patterns after the major lung resection, these findings must be considerable thing.

[A case of mediastinal goiter with hyperthyroidisms].

A 65-years-old woman admitted to the hospital in order to treat of the mediastinal tumor, but she suffered from palpitation, slight fever, sweating, uneasiness, sleeplessness and weightloss. On the physical examination, she was experiencing tachycardia, fevering (37.2 approximately 37.6 degrees C). Skin was moist but had no exophtalmos or neck tumor. Chest X-ray showed an abnormal shadow in the upper mediastinum. On chest CT, a tumor mass (9 x 5 x 4 cm) with cystic regions and scattered calcifications occupied from anterior to posterior mediastinum. The tumor compressed trachea to the left and right brachiocephalic vein and SVC to the right. Lower portion of the tumor intruded into behind of the trachea. Lymph node swelling of mediastinum was also detected. Results of general laboratory examination were within normal limits. Thyroid function test revealed hyperthyroidism; T3U 58%, free T3 24.4 pg/ml, free T4 6.0 ng/dl and thyroglobulin 967 mg/dl, but TSH was < 0.01 microIU/ml. After daily administration of methimazole (300 mg/day) for 4 weeks, thyroid function became to normal level and symptoms of hyperthyroidism was disappeared. The tumor was completely extirpated with right hemithyroidectomy and lymph node dissection under neck colla incision and median sternotomy. Pathological finding of the tumor showed follicular-fetal adenoma of thyroid with hyaloid degeneration and cystic change. There was no finding suspected of Graves' disease. She is well without any complications for 8 months after operation. Some discussion of the literature was mentioned.

[Usefulness of the preoperative MRI for diagnosis and operative method in a case of cor triatriatum].

A case was 6-year-old female diagnosed as the cor triatriatum. The magnetic resonance imaging synchronized at R wave on the electrocardiogram was performed in order to see the abnormal septum in the left atrium. In the horizontal view, the abnormal septum that divides the left atrium into the accessory left atrial chamber and the true left atrium, was well visualized. This septum lied on the vertical portion. Operation was carried out with the approach through the accessory chamber and the fibromuscular membrane were excised. Preoperative imaging of the MRI was useful and helpful for us to reach to a decision of the surgical approach in this patient.

[Emergency surgical salvage for a type A early thrombosed aortic dissection complicated cardiac tamponade in a 80-year-old-patient].

A 80-year-old woman underwent emergency operation for a type A early thrombosed aortic dissection associated with cardiac tamponade. Her preoperative chest CT (not enhanced) showed high density area in the false lumen that indicated early thrombosis and the projection of true lumen at antero-left-lateral portion of ascending aorta that means "ulcer-like projection" called on aortogram. After the relief of the cardiac tamponade by pericardiocenthesis, we emergently performed the graft replacement of the ascending aorta under the extracorporeal circulation combined with selective cerebral perfusion. Her postoperative course was uneventful and satisfactory.

[Autologous blood transfusion in cardiac surgery over 70-year-old patients].

We discussed the problems for autologous blood transfusion particularly in the preoperative blood donation about the patients over 70-year-old who underwent cardiac surgery in contrast with the younger patients. Following results were obtained: 1) Because aged patients have the tendency of anemia before predonation, full storage of blood donation could not be successed. 2 of 8 over 70-year-old patients were able to do the preoperative phlebotomy, and their mean volume were 355 gram as whole blood. On the other hand, 96% patients in younger group were phlebotomized preoperatively, and their mean value of storaged blood volume were 757 gram. 2) As the examinations about the iron-related parameters, not all aged patients were iron deficiency status. Their reticulocyte counts were nearly equal level to the younger group and plasma concentration of erythropoietin were higher in the aged patients than that in the younger group. These results indicate that erythropoiesis in the bone marrow was deteriorated in the aged patients. 3) In aged patients, all of them were required homologous blood transfusion at their perioperative terms. We thought that they have had the anemia before preoperation and our tolerable, allowable level to the postoperative anemia was not lower in the aged patients as against to the younger group. 4) We performed the autologous plasma donation with the membranous plasma separator added to the whole blood donation. It was easy and safe method, and circulatory indices were not changed before and after plasma-separation even in the aged patients. These autologous plasma were usefully administered as the volume expander postoperatively.

Delayed hemolytic transfusion reaction with anti-Jkb erythrocyte antibody after open heart surgery.

A patient suffering from delayed hemolytic transfusion reaction with anti-Jkb erythrocyte antibody after open heart surgery is reported on. On preoperation evaluation, a 42-year-old woman who had never been transfused exhibited a negative erythrocyte autoantibody. After the operation of aortic valve replacement and open mitral commisurotomy, she developed a severe hemolytic anemia with a positive rare anti-Jkb erythrocyte antibody on the 14th postoperative day. Precautions are discussed which need to be taken to distinguish delayed hemolytic transfusion reaction from mechanical hemolysis caused by extracorporeal circulation and prostheses.

[A case of malignant thymoma associated with myasthenia gravis, pure red cell aplasia and high serum level of SCC antigen].

We present a case of 43-year-old man with pure red cell aplasia appearing 8 years after thymothymectomy. He underwent an operation and postoperative radiotherapy for malignant thymoma associated with myasthenia gravis in 1983. In 1991 high serum level of SCC antigen was noted and a metastatic tumor was found in the retroperitoneal region. After removal of the tumor pure red cell aplasia developed, which responded to steroid therapy. The serum level of SCC antigen is still abnormally high.

A single amino acid substitution converts cytochrome P450(14DM) to an inactive form, cytochrome P450SG1: complete primary structures deduced from cloned DNAS.

Genes for lanosterol 14-demethylase, cytochrome P450(14DM), and a mutated inactive cytochrome P450SG1 were cloned from S. cerevisiae strains D587 and SG1, respectively. A single nucleotide change resulting in substitution of Asp for Gly-310 of cytochrome P450(14DM) was found to have occurred in cytochrome P450SG1. In this protein the 6th ligand to heme iron is a histidine residue instead of a water molecule, which may be the ligand for the active cytochrome P450(14DM). Molecular models of the active sites of the cytochrome P450(14DM) and cytochrome P450SG1 were built by computer modeling on the basis of the known structure of that of cytochrome P450CAM whose crystallographic data are available. The mechanisms which may cause a histidine residue to gain access to the heme iron are discussed.