Age-related changes in tongue pressure during swallowing.

Although swallowing movement is known to change with aging, age-related differences in the tongue pressure for propelling a bolus from the oral cavity into the pharynx have yet to be investigated in a physiological condition. We hypothesized that tongue pressure during swallowing changed with aging and, using a 0.1-mm-thick sensor sheet with 5 measuring points, measured it while a 15-mL quantity of water was swallowed by young and elderly dentate individuals. Both groups showed a similar order of tongue pressure production at each point. However, the elderly group showed longer duration at each point, lower maximal magnitude in the anterio-median part of the hard palate, and higher magnitude in the circumferential parts of the hard palate than the young group. These results provide the first quantitative evidence of the age-related changes in tongue movement during natural swallowing, which could be attributed to muscle weakening and morphological changes in the oropharynx.

Direct measurement of nitric oxide during experimental cardiopulmonary bypass.

We developed a system to measure nitric oxide (NO) concentration during cardiopulmonary bypass in anaesthetized pigs (n = 6). A T-shaped connector, attached to an NO sensor, was mounted in the extracorporeal circuit at two measuring sites: proximal to the membrane oxygenator (venous side) and distal to the arterial line filter (arterial side). After performing a preliminary validation study, we measured plasma NO concentration before and during total cardiopulmonary bypass circulation (non-pulsatile flow 1.5 l/min) and without pulmonary ventilation. After establishing bypass, PaO2 was 318 - 393 mmHg; when PaO2 was decreased to 80 - 100 mmHg, plasma NO concentration in the arterial circuit fell by 39.2 +/- 15.6 nM. There was no observable change in plasma NO concentration at the venous circuit. This new system could be useful in monitoring NO concentration during cardiac surgery with cardiopulmonary bypass, and for understanding the possible pathophysiological roles of hyper-nitric oxaemia in cardiopulmonary bypass-related cardiovascular complications.

Glucosylceramide accumulates preferentially in lamellar bodies in differentiated keratinocytes.

BACKGROUND: Sphingolipids, e.g. ceramide (Cer), glucosylceramide (GlcCer) and sphingomyelin (SM), are important bulk constituents of plasma membranes in mammalian cells. In addition, these lipids are also enriched in certain intracellular organelles, as well as in the epidermal lamellar bodies (LBs) of differentiating keratinocytes (KCs). Epidermal Cer, which comprises a heterogeneous family of at least 10 members, is a key component of the stratum corneum (SC) lipids, and regulates permeability barrier function. Levels of GlcCer, but not SM, significantly increase during epidermal differentiation, and then both GlcCer and SM are enzymatically hydrolysed to Cer at and just above the transition from the stratum granulosum to the SC. OBJECTIVES: To determine: (i) whether the GlcCer contained in different pools, i.e. the membrane fraction or the LB fraction, has different metabolic fates; and (ii) whether specific molecular species of GlcCer localize to distinct subcellular pools. METHODS: To study the metabolic fate of specific molecular fractions of GlcCer and Cer, we first ascertained the full spectrum of molecular species present in cultured normal human KCs (CHK) in a differentiated condition as shown in vivo in epidermis. Cer species were analysed in CHK using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Next, the metabolic fate of the GlcCer was studied by pulse-labelling of CHK with L-[14C]-serine. RESULTS: The GlcCer of undifferentiated KCs comprised GlcCer B and Cer NS (or Cer 2), which contain nonhydroxy fatty acid (FA) as the amide-linked FA, while differentiated KCs displayed further heterogeneity of both GlcCer and Cer, including the presence of acylGlcCer and acylCer. The metabolic fates of these sphingolipids were determined. The GlcCer B level decreased over 2 days and then plateaued between days 3 and 5 following pulse-labelling of sphingolipids for 24 h. As GlcCer B declined, Cer NS (Cer 2) increased in a similar time-dependent manner. In contrast, both acylGlcCer and acylCer increased continuously in parallel over this experimental period. CONCLUSIONS: Distinct GlcCer pools segregated to those that were either hydrolysable or nonhydrolysable in differentiated KCs. We assume that the latter pool appears to be LB enriched, and also sequestrates acylGlcCer from other cellular membrane fractions.

beta2-adrenergic receptor stimulation-induced immunosuppressive effects possibly through down-regulation of co-stimulatory molecules, ICAM-1, CD40 and CD14 on monocytes.

We examined the effects of beta2-adrenergic receptor (beta2-AR) agonists on the expression of co-stimulatory molecules on lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells. The study found that beta2-AR agonists inhibited the expression of intercellular adhesion molecule-1 (ICAM-1), CD40 and CD14 on monocytes, and that AR agonist activity was antagonized by the selective beta2-AR antagonist, butoxamine. The selective beta2-AR agonists salbutamol and terbutaline induced a similar co-stimulatory molecule expression pattern. The LPS-induced production of tumour necrosis factor-alpha was inhibited by AR agonists, and this was also antagonized by butoxamine, and mimicked by salbutamol and terbutaline. The AR agonists also inhibited T-cell proliferation through beta2-AR stimulation. This study clearly demonstrated that endogenous catecholamines elicited immunosuppressive effects through beta2-AR stimulation, possibly due to down-regulation of the expression of ICAM-1, CD40 and CD14 on monocytes. These results suggested that the sympathetic nervous system might regulate the T-helper cell balance via the peripheral end-effectors of the stress system.

[Surgical treatment of thymic carcinomas].

Five cases of surgically treated thymic carcinoma are reported. The patients (4 men and a woman) ranged in age from 46 to 76 years old with a mean of 64.6. Four patients were asymptomatic and an abnormal shadow on X-ray films was noted. One remaining patient suffered from hoarseness. One patient had stage II disease and the others had stage III. Surgical tumor resection was performed in all cases. Only 1 patient among the 5 underwent a successful complete resection. Histological examinations of the resected specimens revealed squamous cell carcinoma of thymus. Four specimens were poorly differentiated and 1 is moderately differentiated carcinoma. All patients received radiation therapy post operatively. Three patients are alive without any recurrence 6, 8 and 109 months after the surgery. Thymic carcinomas are frequently invasive or metastatic at the time of diagnosis. But poorly differentiated group, in squamous cell carcinoma, mucoepidermoid carcinoma and besaloid carcinoma, are characterized by a low incidence of local recurrence and distant metastasis. They also have a good sensitivity for the radiation. Therefore complete surgical resection combined with postoperative radiation therapy should be a choice in treating thymic carcinomas. We considered that complete resection and postoperative radiation therapy is a curative therapy for thymic carcinomas.

Platelet activity of residual blood remained in the cardiopulmonary bypass circuit after cardiac surgery.

AIM: We measured the platelet count and platelet function in residual blood in the cardiopulmonary bypass (CPB) circuit after cpb and compared them with data before CPB operation. METHODS: The subjects included 34 cases of patients subjected to CPB surgery. The residual blood was concentrated by ultrafiltration after CPB, collected in the bag and the platelet count and platelet activity was measured. ADP 2, 5, 10 microM was used as agonists and measurement was made by turbidimetry. RESULTS: The mean value of the platelet count was 18.3+/-5.65x10(4)/mm(3) before surgery and 17.2+/-8.39x10(4)/mm(3) in the residual blood, there is no difference. Concerning the platelet aggregation activity, the maximum aggregation rate decreased significantly with ADP 2 microM from 47.4+/-19.6% before surgery to 27.1+/-17.2% in the residual blood (p<0.01). Likewise, it decreased significantly with ADP 5 and 10 microM. The reduction rate of the platelet aggregation activity was higher in the group of not less than 100 minutes compared with the group of less than 100 minutes, but no significant difference was found. CONCLUSION: Autotransfusing whole blood per se without the "cell saver" treatment is more advantageous to keep hemostasis function after surgery since many platelets having the aggregation activity exist in residual blood in the CPB circuit.

[Ventricular free wall re-rupture after surgical treatment of ventricular free wall rupture due to acute myocardial infarction; report of a case].

An in-hospital 72-year-old male with complaint of anterior chest pain was presented with shock. Pericardial effusion was confirmed by echocardiography, and therefore, he was brought to the operating room immediately with diagnosis of ventricular free wall rupture. The repair was performed using fibrin glue, fibrin sheet, and pericardial patch. His post-operative course was uneventful until massive bleeding came through the chest tube on the 5th day from the initial surgery. The emergency sternotomy was made again for hemostasis. In the re-operation, an approximately 20 mm laceration along the proximal circumflex artery was found and this was successfully repaired with 2 pledgetted horizontal mattress sutures. It is important and necessary to treat a postoperative patient taking care of re-rupture.

An outbreak of allergy-like food poisoning.

Eight cases of allergy-like food poisoning resulting from the ingestion of yellowfin tuna, which had been kept in stock for 10 days prior to being cooked, are described. The main symptoms were headaches, facial flushing and palpitation. Samples of the ingested fish were analyzed for histamine content, and a high level of histamine was confirmed (310 mg/100 g of fish). Corticosteroids were given to 3 patients who exhibited dyspnea or persistent symptoms, while the remaining patients improved without medication. In situations where allergy-like clinical features are present after the ingestion of food, the possibility of allergy-like food poisoning should be recognized and included in a differential diagnosis.

Portal and mesenteric vein and inferior vena cava thrombosis associated with antiphospholipid syndrome.

We report a 48-year-old man with thrombosis of the portal and superior mesenteric vein and inferior vena cava associated with primary antiphospholipid syndrome (APS). Primary APS was diagnosed by a positive reaction with anticardiolipin antibody (aCL) and the absence of any evidence suggesting the presence of other disease states known to be associated with aCL. A coeliac angiography showed obstruction of the portal and superior mesenteric vein with prominent collaterals and cavernous transformation. Femoral vein angiography showed total obstruction of the external iliac vein and inferior vena cava, and dilation of the pelvic veins, with contrast medium in the lumbar vein. This case is noteworthy as a report of primary APS accompanied by extensive abdominal and pelvic venous thrombosis.

Epidermal sphingomyelins are precursors for selected stratum corneum ceramides.

Epidermal ceramides (Cer) comprise a heterogeneous family of seven species, including two unique omega-hydroxylated Cer, that are key components of the stratum corneum (SC) intercellular lamellar membranes responsible for the epidermal permeability barrier. Although both glucosylceramide (GlcCer) and the phospho-sphingolipid sphingomyelin (SM) are potential precursors of SC Cer, based on reported chemical structures of epidermal GlcCer and SC Cer, it is assumed that all major subfractions of SC Cer are generated from lamellar body-derived GlcCer. Yet, we and others have shown that SM-derived Cer are required for normal barrier homeostasis. Moreover, two pools of SM, one from plasma membrane, the other from lamellar body-derived contents, are potentially available for Cer production. To clarify the role of SM as a potential precursor of bulk or specific SC Cer, we compared Cer moieties in epidermal SM, Cer generated from epidermal SM by sphingomyelinase treatment, Cer within SC, and Cer that persist in Gaucher SC, where GlcCer cannot generate Cer due to an absence of beta-glucocerebrosidase. Using gas chromatography-mass spectrometry, fast atom bombardment-mass spectrometry, and nuclear magnetic resonance for Cer characterization, epidermal SM comprise three major subfractions with distinctive amide-linked (N-acyl) fatty acid (FA) compositions: that is, either long-chain FA (SM-1; C(22;-26)), short-chain FA (SM-2; primarily C(16)), and short-chain alpha-hydroxy FA (SM-3; C(16;-18)). In contrast, only trace quantities of omega-hydroxy FA were present. For each SM subfraction, the sphingoid base was either sphingosine or sphinganine, but phytosphingosine was not detected. Comparison of these SM with corresponding sphingomyelinase-generated epidermal Cer and SC Cer revealed that the Cer moieties of SM-1 and SM-3 are equivalent to Cer 2 (NS) and Cer 5 (AS), respectively. Moreover, both Cer 2 and Cer 5 occurred in Gaucher SC, whereas other Cer subfractions did not occur. These results indicate that two epidermal SM, that is, SM-1 and SM-3, are important precursors of two corresponding Cer in mammalian SC, that is, Cer 2 and Cer 5, but other Cer species, including the omega-hydroxy Cer species, do not derive from SM.

[A case of non-small-cell lung cancer successfully treated using combination chemotherapy with CDDP and vinorelbine].

A 67-year-old woman presented to our hospital with a chief complaint of bloody sputum. A plain chest X-ray a CT scan revealed a tumor shadow 3 cm in size in the middle lobe of the right lung, multiple nodular shadows in the bilateral lung fields and enlarged hilar and mediastinal lymph nodes. A tumor biopsy done under bronchoscopy revealed poorly differentiated adenocarcinoma of the lungs (cT2N3M1). She was given two courses of combination therapy consisting of cisplatin (80 mg/m2) and vinorelbine (20 mg/m2). The primary tumor in the middle lobe of the right lung and the lung metastases were markedly reduced in size, and a complete response was obtained. The only adverse events were grade 4 neutropenia and grade 2 nausea and vomiting.

[Combined valvular and coronary artery surgery].

Between 1990 and 1999, 78 patients underwent combined valvular coronary artery operation. Aortic valve disease was present in 49 patients, mitral valve disease in 23 patients, aortic and mitral valve disease in 6 patients. The average age was 67 years. Twelve patients had had a previous myocardial infarction. The average number of grafts inserted was 1.82 per patients, and the average number of artery grafts inserted was 0.96 per patients. The most number of grafts were placed prior to valve replacement or plasty. And periods of myocardial ischemia were kept at a minimum by coronary perfusion through free grafts. Preoperative mortality was 1.3%. And event fee ratio after operation was 95% (mean follow up 42 month). Therefore the operative risk of combined surgery is, in general, low and the long term results are favorable.

[A case report of aneurysm of the ductus arteriosus combined with mitral regurgitation].

A case with the giant aneurysm of the ductus arteriosus combined with severe mitral regurgitation is reported. 58-year-old male underwent MVR and patch closure of the ductal orifice for staged operation. The first operation was MVR and patch closure of the PDA orifice of the pulmonary artery end using retrograde cerebral perfusion (RCP) with deep hypothermic circulatory arrest (DHC). The second operation was performed on 3 months after the first operation using left thoracotomy approach, and patch closure of the ductal orifice via the aorta using RCP with DHC was performed. Upon following-up examination, the patient is now doing well 20 months after the initial surgery.

[Surgical treatment of intracardiac tumors in 25 patients].

For most intracardiac tumors, operation is the only means of therapy. In our institute, we have aggressively performed operation for intracardiac tumors regardless of histological type because resection for tumor had a beneficial effect on the hemodynamics with congestive heart failure. Twenty-five cases of cardiac tumors were operated upon from 1980 through 1998. The follow-up period ranged from 2 months to 19 years. The histological diagnoses of the tumors were as follows: benign tumors 24 (myxoma 21, papillary fibroelastoma 1, fibroma 1, angiomyolipoma 1) and malignant tumor (angiosarcoma 1). There was one hospital death in this series. In the New York Heart Association classification, the cardiac performances of intracardiac benign tumors after operation were Class I or II. The results of surgical treatment of intracardiac benign tumors were satisfactory both in short-term and in long-term. On the other hand the long term result of malignant tumor was extremely poor. A patient with angiosarcoma died 8 months later due to bone metastasis.

Identification of cDNA encoding cytochrome c oxidase subunit 5c (COX5c) from rice: comparison of its expression with nuclear-encoded and mitochondrial-encoded COX genes.

Little is presently known about the nuclear-encoded genes for cytochrome c oxidase (COX) in higher plants. In rice, only the nuclear-encoded COX5b gene has been reported. To understand the relationship between the expression of nuclear-encoded and mitochondrial-encoded COX genes in rice, we first characterized a cDNA encoding one of the other nuclear COX genes, COX5c, which encodes 63 amino acids. The deduced amino acid sequence of COX5c from rice was highly homologous to that from sweet potato. Genomic Southern hybridization indicated that the rice COX5c subunit is encoded by a single copy of the COX5c gene. Furthermore, we compared the expression patterns of the nuclear-encoded COX5c and COX5b genes with the expression pattern of the mitochondrial-encoded COX1 gene among several organs by Northern blot analysis. The results suggested that regulatory systems of expression between the nuclear-encoded and the mitochondrial-encoded COX genes are different among different organs in rice.

[Clinical study of emergency coronary artery bypass surgery].

Between January, 1996 and December, 1998, 29 patients were undergone emergency coronary artery bypass grafting (CABG) in our institute. Age ranged 34 to 85 years (mean 65 +/- 11 years, male:female = 25:4). Of 29 emergency cases, 3 were hospital death. Hospital mortality rate was 10.7%, which was significantly higher than the hospital mortality of elective CABG (1.4%) during the same period. The necessity of IABP before CABG was 72% in emergency cases (elective surgery: 0%). Thus the use rate of arterial grafts were 86.2% in emergency cases (elective surgery: 100%), the patency of the arterial grafts were 100%. It is important to make stable condition of the patients before the operation, and therefore it is important to make contact closely with the cardiologists for making stable condition and for lowering the operative mortality. And, we should use arterial grafts for the long term result as much as possible if it is an urgent operation.

[New screening method for coagulation abnormality including AT III deficiency during CABG].

In our institute, 1 ml of heparin is administered to the patients undergoing CABG before dissection and mobilization of the internal thoracic arteries (ITAs) and/or right gastroepiploic artery (GEA) to prevent possible thrombosis or coagulation tendency. Two patients with AT III deficiency underwent CABG and one of them died. The aim of this study is to know whether ACT check before and after administration of 1 ml of heparin is useful as a screening test of coagulation abnormalities including AT III deficiency. One hundred patients (84 males and 16 females) undergoing CABG were studied. Age ranged from 41 to 79 years (mean 64.8 +/- 8.0 years). One ml of heparin was administered to all the patients before ITAs and/or GEA were dissected and mobilized. ACT was doubly checked before (control ACT: c-ACT) and after (heparinized ACT: h-ACT) administration of heparin. ACT extension was defined as follows: ACT extension = (c-ACT)-(h-ACT). Mean c-ACT was 124 +/- 12 sec., h-ACT 188 +/- 26 sec. and ACT extension 64 +/- 24 sec. There were only 3 cases which ACT extension were less than 30 sec.: two of them were combined with AT III deficiency and the other was due to insufficient administration of heparin. In conclusion, examination of ACT after 1 ml administration of heparin is new, simple and convenient screening method for coagulation abnormalities including AT III deficiency during CABG.

Crystal structure determinations of oxidized and reduced plastocyanin from the cyanobacterium Synechococcus sp. PCC 7942.

The crystal structures of oxidized and reduced plastocyanins from Synechococcus sp. PCC 7942 have been determined at 1.9 and 1.8 A resolution, respectively, at pH 5.0. The protein consists of only 91 amino acid residues, the smallest number known for a plastocyanin, and apparently lacks the mostly conserved acidic patch that is believed to be important for recognition with electron-transfer partners. The protein has two acidic residues, Glu42 and Glu85, around Tyr83, which is thought to be a possible conduit for electrons, but these are neutralized by Arg88 and Lys58. Residue Arg88 interacts with Tyr83 through a pi-pi interaction in which the guanidinium group of the former completely overlaps the aromatic ring of the tyrosine. Reduction of the protein at pH 5.0 causes a lengthening of one Cu-N(His) bond by 0.36 A, despite the small rms deviation of 0.08 A calculated for the backbone atoms. Moreover, significant conformational changes of Arg88 and Lys58, along with the movement of a water molecule adjacent to the OH group of Tyr83, were observed on reduction; the guanidinium group of Arg88 rotates by more than 11 degrees, and the water molecule moves by 0.42 A. The changes around the copper site and the alterations around Tyr83 may be linked to the reduction of the copper.

Crystallization and preliminary X-ray analysis of plastocyanin from cyanobacterium Synechococcus sp. PCC 7942.

A plastocyanin from the cyanobacterium Synechococcus sp. PCC 7942 has been crystallized in two different forms by hanging-drop vapour diffusion with ammonium sulfate as precipitant. Form I is hexagonal, space group P61 or P65, with unit-cell dimensions a = b = 34.62 and c = 107.22 A. Form II is tetragonal, space group P41 or P43, with unit-cell dimensions a = b = 43.05 and c = 56.94 A. Form I crystals diffract to 2.5 A using graphite-monochromated Cu Kalpha radiation from a Rigaku RU-300 rotating-anode generator operated at 40 kV and 100 mA. Form II crystals diffract to 1.9 A using synchrotron radiation at beamline BL6A of the Photon Factory (KEK). Molecular-replacement calculations using the structure of plastocyanin from Ulva pertusa have been performed.